Abstract

Background

Understanding the constraints that operate in mammalian gene promoter sequences is
of key importance to understand the evolution of gene regulatory networks. The level
of promoter conservation varies greatly across orthologous genes, denoting differences
in the strength of the evolutionary constraints. Here we test the hypothesis that
the number of tissues in which a gene is expressed is related in a significant manner
to the extent of promoter sequence conservation.

Results

We show that mammalian housekeeping genes, expressed in all or nearly all tissues,
show significantly lower promoter sequence conservation, especially upstream of position
-500 with respect to the transcription start site, than genes expressed in a subset
of tissues. In addition, we evaluate the effect of gene function, CpG island content
and protein evolutionary rate on promoter sequence conservation. Finally, we identify
a subset of transcription factors that bind to motifs that are specifically over-represented
in housekeeping gene promoters.

Conclusion

This is the first report that shows that the promoters of housekeeping genes show
reduced sequence conservation with respect to genes expressed in a more tissue-restricted
manner. This is likely to be related to simpler gene expression, requiring a smaller
number of functional cis-regulatory motifs.